Maxine Deborrah Hyde: First Female Graduate of Case Western Reserve University's Neurologic Surgery Residency Program and Second Black Female Neurosurgeon in the United States.

BACKGROUND: The historical diversity gap in the neurosurgical workforce persists to this day. Women, despite constituting over half of the yearly total of medical school graduates, comprise only 6% of certified practicing neurosurgeons in the United States. Furthermore, Black Americans make up under 4% of U.S. neurosurgeons, despite making up around 14% of the national population. The purpose of this account is to highlight the life and career of Dr. Maxine Deborrah Hyde and illustrate the importance and necessity of diversity and inclusivity in advancing the field of neurosurgery. Through this paper, we aspire to encourage the development of new diversity initiatives. METHODS: Original scientific and bibliographic materials of Hyde were examined, and an extensive analysis of her life was compiled. RESULTS: Despite growing up during the era of Jim Crow, Dr. Hyde persevered and became the valedictorian of Oak Park High School. As a first-generation college student at Tougaloo College, she later earned her MS from Cleveland State University. Dr. Hyde graduated with honors from Case Western Reserve University School of Medicine in 1977. Thereafter, she became the first female and first Black graduate of Case Western's neurosurgery residency and the second Black woman to receive certification from the American Board of Neurological Surgery. Later in life, Dr. Hyde established the Beacon of Hope Scholarship Foundation to assist disadvantaged students in overcoming educational barriers. CONCLUSIONS: Dr. Hyde was a trailblazer who overcame systematic barriers and paved the way for future generations of aspiring neurosurgeons.

A survey of exposure to the use of Xiaflex for the treatment of Peyronie's disease among United States urology residency programs.

Xiaflex® (collagenase clostridium histolyticum) is a Food and Drug Administration-approved treatment for patients with Peyronie's disease. Despite its approval and implementation, there is concern that urologists in training are offered minimal exposure to its use. Thus, the purpose of this study was to evaluate the exposure of urology residents to Peyronie's disease and its management, particularly Xiaflex®. A Google Forms survey regarding the exposure of residents to Peyronie's disease and use of Xiaflex® was created and disseminated through email to urology programs. Overall, 47 institutional responses were received. At 45 institutions (95.7%), residents receive training in directly evaluating and caring for patients with Peyronie's disease. At 46 institutions (97.9%), residents receive training in observing and/or performing surgical procedures for Peyronie's disease. Residents at 31 institutions (66.0%) receive observational or procedural training for non-surgical management of Peyronie's disease, specifically Xiaflex®. Residents receive non-surgical training from an academic faculty who is fellowship trained in sexual medicine at 25 institutions and an academic faculty not trained in sexual medicine at six institutions. There exists a glaring disparity in residency exposure to Xiaflex®. Further research is warranted to elucidate how programs can provide residents with further exposure to the use of Xiaflex® in patients with Peyronie's disease.

COVID-19 Vaccination and Reproductive Health: a Comprehensive Review for Healthcare Providers.

With all the current misinformation on social media platforms about the COVID-19 vaccine and its potential effects on fertility, it is essential for healthcare providers to have evidenced-based research to educate their patients, especially those who are trying to conceive, of the risks to mothers and fetuses of being unvaccinated. It is well known that COVID-19 infection puts pregnant women at higher risk of complications, including ICU admission, placentitis, stillbirth, and death. In February of 2021, the American College of Obstetricians and Gynecologists (ACOG), the American Society for Reproductive Medicine (ASRM), and the Society for Maternal-Fetal Medicine (SMFM) released a statement denying any link between COVID vaccination and infertility. ASRM later confirmed and stated that "everyone, including pregnant women and those seeking to become pregnant, should get a COVID-19 vaccine". In this review, we aim to provide a compilation of data that denies any link between vaccination and infertility for healthcare providers to be able to educate their patients based on evidence-based medicine. We also reviewed the effect of COVID-19 virus and vaccination on various parameters and processes that are essential to obtaining a successful pregnancy.

Calcified spinal meningiomas: a systematic review of clinical characteristics, treatment strategies, and outcomes.

BACKGROUND: Calcified meningiomas involving the spine are rare but can pose significant surgical challenges. We systematically reviewed the literature on calcified spinal meningiomas. METHODS: PubMed, EMBASE, Web-of-Science, and Scopus databases were searched to include studies reporting clinical data of patients with calcified spinal meningioma. Included articles were analyzed for symptoms, imaging, spine level of the tumor, tumor location relative to the spinal cord, calcification status, treatment regimen, recurrence, progression-free survival, and outcomes. RESULTS: A total of 35 articles encompassing 94 patients were included. Most patients were female (90.4%), presenting with lower extremity weakness (44%) and/or lower extremity paresthesia (38.1%). Most calcified spinal meningiomas occurred in the thoracic spine (82%) and on the dorsal (33.3%) or ventral (27.2%) side relative to the spinal cord. Most tumors were intradural (87.2%). Histologically, most calcified spinal meningiomas were WHO grade I (97.4%) and psammomatous (50.7%). Most tumors demonstrated macroscopic calcification (48.9%). Most patients underwent gross total resection (91.5%) through a posterior approach (100%). Two patients (2.1%) received adjunctive radiotherapy. The most common treatment related complication was CSF leakage. Post-operatively, most patients demonstrated symptomatic improvement (75.5%) and 2 (2.1%) had local tumor recurrence. CONCLUSIONS: Calcified spinal meningiomas are uncommon but benign entities. These neoplasms tend to adhere to surrounding tissues and nerves and, thus, can be surgically challenging to remove. In most patients, safe gross total resection remains the standard of care, but accurate surgical planning is necessary to reduce the risks of postoperative complications.

Impact of obesity on complications and surgical outcomes after adult degenerative scoliosis spine surgery.

OBJECTIVE: To compare perioperative outcomes of obese versus non-obese adult patients who underwent degenerative scoliosis spine surgery. METHODS: 235 patients who underwent thoracolumbar adult spinal deformity (ASD) surgery (≥4 levels) were identified and categorized into two cohorts based on their body mass indices (BMI): obese (BMI ≥30 kg/m2; n = 81) and non-obese (BMI <30 kg/m2; n = 154). Preoperative (demographics, co-morbidities, American Society of Anesthesiologists (ASA) score and modified frailty indices (mFI-5 and mFI-11)), intraoperative (estimated blood loss (EBL) and anesthesia duration), and postoperative (complication rates, Oswestry Disability Index (ODI) scores, discharge destination, readmission rates, and survival) characteristics were analyzed by student's t, chi-squared, and Mann-Whitney U tests. RESULTS: Obese patients were more likely to be Black/African-American (p < 0.05, OR:4.11, 95% CI:1.20-14.10), diabetic (p < 0.05, OR:10.18, 95% CI:4.38-23.68) and had higher ASA (p < .01) and psoas muscle indices (p < 0.0001). Furthermore, they had greater pre- and post-operative ODI scores (p < 0.05) with elevated mFI-5 (p < 0.0001) and mFI-11 (p < 0.01). Intraoperatively, obese patients were under anesthesia for longer time periods (p < 0.05) with higher EBL (p < 0.05). Postoperatively, while they were more likely to have complications (OR:1.77, 95% CI:1.01 - 3.08), had increased postop days to initiate walking (p < .05) and were less likely to be discharged home (OR:0.55, 95% CI:0.31-0.99), no differences were found in change in ODI scores or readmission rates between the two cohorts. CONCLUSIONS: Obesity increases pre-operative risk factors including ASA, frailty and co-morbidities leading to longer operations, increased EBL, higher complications and decreased discharge to home. Pre-operative assessment and systematic measures should be taken to improve peri-operative outcomes.

Assessing the quality and readability of online content on shock wave therapy for erectile dysfunction.

Patients are becoming increasingly reliant on online platforms for obtaining health information. Previous research has shown that the quality of information available on the internet regarding novel medical therapies is generally poor and frequently misleading. Shock wave therapy represents a novel restorative therapy for erectile dysfunction (ED) that has recently gained attention. We hypothesised that online sources regarding shock wave therapy for ED would be fraught with misleading claims and unreliable health information. Our objective was to evaluate the quality and readability of online medical information on shock wave therapy as a treatment for ED. Websites were generated using a Google search of 'shock wave therapy for erectile dysfunction' with location filters disabled. Readability was analysed using the Readable software (Readable.com, Horsham, United Kingdom). Quality was assessed independently by three reviewers using the DISCERN tool. Articles were subdivided into those from private clinic websites and those from universities or news media websites. Statistical analysis was conducted using the Student's t test. Nine articles that resulted from the Google search had mean readability scores as follows: Flesch-Kincaid grade level (10.8), Gunning-Fog Index (13.67), Coleman-Liau Index (12.74), Simple Measure of Gobbledygook (SMOG) Index (13.33), FORCAST Grade Level (11.33), and Automated Readability Index (11.08). The mean Flesch Reading Ease score was 46.4. The articles had a mean DISCERN score of 3.1, suggesting 'moderate quality' content. Articles from universities (n = 2) or news sources (n = 3) had significantly higher DISCERN scores than articles from private medical practices (n = 4). There was no difference in readability scores between the groups. Articles from private clinics are just as readable as those from universities or news media, but they are significantly more biased and misleading. The current online material relating to shock wave therapy for ED may not adequately inform patients in their medical decisions making, thereby necessitating closer collaboration between the sources disseminating information and urologists.

Development and validation of a need-based integrated yoga program for cancer patients: a retrospective study.

CONTEXT AND AIM: Complementary and alternative therapies (CAM) are gaining popularity amongst patients as add on to conventional medicine. Yoga stands third amongst all CAM that is being used by cancer patients today. Different schools of yoga use different sets of practices, with some using a more physical approach and many using meditation and/or breathing. All these modules are developed based on the needs of the patient. This paper is an attempt to provide the basis for a comprehensive need based integrative yoga module for cancer patients at different stages of treatment and follow up. In this paper, the holistic modules of the integrated approach of yoga therapy for cancer (IAYTC) have been developed based on the patient needs, as per the observations by the clinicians and the caregivers. Authors have attempted to systematically create holistic modules of IAYTC for various stages of the disease and treatment. These modules have been used in randomized trials to evaluate its efficacy and have shown to be effective as add-on to conventional management of cancer. Thus, the objective of this effort was to present the theoretical basis and validate the need based holistic yoga modules for cancer patients. MATERIALS AND METHODS: Literature from traditional texts including Vedas, Ayurveda, Upanishads, Bhagavat Gita, Yoga Vasishtha etc. and their commentaries were looked into for references of cancer and therapeutic directives. Present day scientific literature was also explored with regards to defining cancer, its etiopathology and its management. Results of studies done using CAM therapies were also looked at, for salient findings. Focused group discussions (FGD) amongst researchers, experienced gurus, and medical professionals involved in research and clinical cancer practice were carried out with the objectives of determining needs of the patient and yoga practices that could prove efficient. A list of needs at different stages of conventional therapies (surgery, chemotherapy and radiation therapy) was listed and yoga modules were developed accordingly. Considering the needs, expected side effects, the energy levels and the psychological states of the participants, eight modules evolved. RESULTS: The results of the six steps for developing the validated module are reported. Step 1: Literature review from traditional yoga and ayurveda texts on etiopathogenesis and management of cancer (arbuda), and the recent literature on cancer stem cells and immunology of cancer. Step 2: Focused group discussions and deliberations to compile the needs of patients based on the expected side effects, energy levels and the psychological state of the patient as observed by the caregivers and the clinicians. Step 3: Content validation through consensus by the experts for the eight modules of IAYTC that could be used as complimentary to conventional management of cancer at different stages during and after the diagnosis was created. Step 4: Field testing for safety and feasibility of the modules through pilot studies. Step 5: Compilation of the results of efficacy trials through RCTs and step 6: A review of our studies on mechanisms to offer evidence for action of IAYTC on psycho-neuro-immunological pathways in cancer. CONCLUSION: The evidence from the traditional knowledge and recent scientific studies validates eight modules of integrated approach of yoga therapy for cancer that can be used safely and effectively as complimentary during all conventional cancer therapies.

Regulation of cystic fibrosis transmembrane conductance regulator single-channel gating by bivalent PDZ-domain-mediated interaction.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent protein kinase- and ATP-regulated chloride channel, the activity of which determines the rate of electrolyte and fluid transport in a variety of epithelial tissues. Here we describe a mechanism that regulates CFTR channel activity, which is mediated by PDZ domains, a family of conserved protein-interaction modules. The Na(+)/H(+) exchanger regulatory factor (NHERF) binds to the cytoplasmic tail of CFTR through either of its two PDZ (PDZ1 and PDZ2) domains. A recombinant fragment of NHERF (PDZ1-2) containing the two PDZ domains increases the open probability (P(o)) of single CFTR channels in excised membrane patches from a lung submucosal gland cell line. Both PDZ domains are required for this functional effect, because peptides containing mutations in either domain are unable to increase channel P(o). The concentration dependence of the regulation by the bivalent PDZ1-2 domain is biphasic, i.e., activating at lower concentrations and inhibiting at higher concentrations. Furthermore, either PDZ domain alone or together is without effect on P(o), but either domain can competitively inhibit the PDZ1-2-mediated stimulation of CFTR. Our results support a molecular model in which bivalent NHERF PDZ domains regulate channel gating by crosslinking the C-terminal tails in a single dimeric CFTR channel, and the magnitude of this regulation is coupled to the stoichiometry of these interactions.

Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated Cl(-) channel that regulates other epithelial transport proteins by uncharacterized mechanisms. We employed a yeast two-hybrid screen using the COOH-terminal 70 residues of CFTR to identify proteins that might be involved in such interactions. The alpha1 (catalytic) subunit of AMP-activated protein kinase (AMPK) was identified as a dominant and novel interacting protein. The interaction is mediated by residues 1420-1457 in CFTR and by the COOH-terminal regulatory domain of alpha1-AMPK. Mutations of two protein trafficking motifs within the 38-amino acid region in CFTR each disrupted the interaction. GST-fusion protein pull-down assays in vitro and in transfected cells confirmed the CFTR-alpha1-AMPK interaction and also identified alpha2-AMPK as an interactor with CFTR. AMPK is coexpressed in CFTR-expressing cell lines and shares an apical distribution with CFTR in rat nasal epithelium. AMPK phosphorylated full-length CFTR in vitro, and AMPK coexpression with CFTR in Xenopus oocytes inhibited cAMP-activated CFTR whole-cell Cl(-) conductance by approximately 35-50%. Because AMPK is a metabolic sensor in cells and responds to changes in cellular ATP, regulation of CFTR by AMPK may be important in inhibiting CFTR under conditions of metabolic stress, thereby linking transepithelial transport to cell metabolic state.

Single-channel properties in endoplasmic reticulum membrane of recombinant type 3 inositol trisphosphate receptor.

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an intracellular Ca(2+)-release channel localized in endoplasmic reticulum (ER) with a central role in complex Ca(2+) signaling in most cell types. A family of InsP(3)Rs encoded by several genes has been identified with different primary sequences, subcellular locations, variable ratios of expression, and heteromultimer formation. This diversity suggests that cells require distinct InsP(3)Rs, but the functional correlates of this diversity are largely unknown. Lacking are single-channel recordings of the recombinant type 3 receptor (InsP(3)R-3), a widely expressed isoform also implicated in plasma membrane Ca(2+) influx and apoptosis. Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. The approach we describe suggests a novel strategy for expression and recording of recombinant ER-localized ion channels in the ER membrane. Ion permeation and channel gating properties of the rat InsP(3)R-3 are strikingly similar to those of Xenopus type 1 InsP(3)R in the same membrane. Using two different two-electrode voltage clamp protocols to examine calcium store-operated calcium influx, no difference in the magnitude of calcium influx was observed in oocytes injected with rat InsP(3)R-3 cRNA compared with control oocytes. Our results suggest that if cellular expression of multiple InsP(3)R isoforms is a mechanism to modify the temporal and spatial features of [Ca(2+)](i) signals, then it must be achieved by isoform-specific regulation or localization of various types of InsP(3)Rs that have relatively similar Ca(2+) permeation properties.

High-efficiency transfer of cystic fibrosis transmembrane conductance regulator cDNA into cystic fibrosis airway cells in culture using lactosylated polylysine as a vector.

To find more efficient vectors for the transfer of CFTR cDNA, lactosylated polylysine was explored for transfer into airway epithelial cells in primary culture. The efficacy and high efficiency of transfection were shown by several criteria: expression of both mRNA and protein for CFTR and the functional correction of the Cl- channel activity. Using specific combinations of agents to enhance the transfection, an efficiency of 90% was obtained as detected by in situ hybridization with digoxigenin-labeled probes generated against exon 14 of CFTR. The highest efficiency was observed by adding E5CA peptide (10 microg) and 5% glycerol to the transfection mixture. The degree of transfection could be controlled by the enhancing agents, thus modulating the efficiency of transfection. The highest level of transfection efficiency is equivalent to that reported for viral vectors. None of the agents or their combinations in the concentrations used were cytotoxic to the primary cells. Antibody pAb3145 was used to detect the expression of the CFTR protein in the cells. When an N-terminal GFP-CFTR fusion gene was used to transfect the CF cells a functional correction of the CFTR Cl- channel was detected by patch-clamp electrophysiology. The high efficiency of CFTR gene transfer with lactosylated polylysine leads to the conclusion that lactosylated polylysine is a promising vector to transfer the CFTR gene into human airway cells in culture.

Alleviation of the temperature-sensitive paralytic phenotype of shibire(ts) mutants in Drosophila by sub-anesthetic concentrations of carbon dioxide.

Cellular mechanisms involved in general anesthesia are unknown. We report here that sub-anesthetic concentrations of carbon dioxide specifically suppress the temperature-sensitive paralytic phenotype of Drosophila shibire(ts) mutants that have a conditional block in synaptic vesicle recycling. Carbon dioxide not only suppresses the onset of temperature-sensitive paralysis, but also rapidly reverses paralysis induced at the restrictive temperature. This effect of CO2 is most pronounced at about 35% in air, and depends on the absolute concentration of available carbon dioxide rather than on the ratio of oxygen to CO2. Other general anesthetics, halothane, N2 or argon do not suppress the paralytic phenotype of shibire significantly at concentrations we tested. Paralysis of the other temperature sensitive paralytic mutants in our collection is not suppressed by carbon dioxide. These behavioral observations are discussed in the light of possible mechanisms underlying paralysis of shi(ts) flies. We suggest that spontaneous seizures induced in shi(ts) flies held at their restrictive temperatures cause vesicle depletion at critical synapses and consequent behavioral paralysis. The effect of subanesthetic concentrations of CO2 may be to depress spontaneous CNS activity, thus raising the threshold temperature at which synaptic vesicle depletion occurs. In support of this model, we show that the threshold temperature for paralysis is reduced in shi(ts) flies when CNS activity is increased by pharmacological or genetic manipulations, and that subanesthetic concentrations of CO2 aggravate, rather than alleviate, the t.s. paralytic phenotype of hypoactive parats flies defective in axonal voltage-gated sodium channels.